Topic: Metastatic Castration Resistant Prostate Cancer

New Standards of Care for Advanced Prostate Cancer

New Standards of Care for Advanced Prostate Cancer

by | Dec 2022

In this 20-minute presentation, William K. Oh, MD, Chief of the Division of Hematology and Medical Oncology at the Mount Sinai Health System and Deputy Director of The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, addresses new standards of care in 2021 for advanced prostate cancer and focuses on non-metastatic castration-resistant prostate cancer (nmCRPC), concluding that apalutamide, enzalutamide, and darolutamide improve MFS in men with nmCRPC by ~2 years; SPARTAN, PROSPER, and ARAMIS established favorable benefit-risk for patients with nmCRPC and PSADT<10 months; and these studies provide the best evidence supporting early treatment. He also focuses on metastatic, hormone-sensitive prostate cancer (mHSPC) and concludes that upfront treatment with either abiraterone + prednisone, apalutamide, enzalutamide, or docetaxel is the standard of care and he asserts that new evidence from PEACE-1 and ARASENS supports triple therapy with a novel hormonal therapy +ADT+docetaxel for chemotherapy patients.

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Industry Perspective: AR-V7 Testing for Men with Advanced Stage Prostate Cancer

by | May 2022

Daniel Shoskes, MD, FRCSC, Medical Director in Medical Affairs for Urologic Oncology at Exact Sciences, and Emeritus Professor of Urology at the Cleveland Clinic, discusses AR-V7 testing for men with metastatic castrate-resistant prostate cancer (mCRPC). He begins by noting that mCRPC cannot be cured, but patients with mCRPC often benefit from multiple lines of sequential therapy. Dr. Shoskes explains that when one therapy fails, choosing the next therapy can often be difficult, in part because patients often prefer AR-targeted therapy over taxanes due to the less burdensome side effect profile of AR-targeted therapies. As a result, even though secondary AR-targeted therapy is only effective 22-46% of the time, AR-targeted therapies are administered back-to-back up to 60% of the time. Dr. Shoskes observes that AR variants are a common cause of AR-targeted therapy resistance, and of those variants, AR-V7 is one of the most common and best understood. He defines AR-V7 as a splice variant of the androgen receptor protein which is active without the ligand binding domain, making it resistant to abiraterone, enzalutamide, and apalutamide. Dr. Shoskes then introduces the Oncotype DX AR-V7 Nucleus Detect assay, which he argues can help clinicians quickly direct their mCRPC patients toward the right treatment. He explains that the Nucleus Detect assay detects the AR-V7 protein in the nucleus of circulating tumor cells, is predictive of resistance to AR-targeted therapies, provides easy-to-interpret and actionable results, and only requires a simple blood draw. Dr. Shoskes highlights that the Nucleus Detect assay has been validated in three independent studies, all of which found that it to be predictive of non-response to AR-targeted therapy. He concludes by discussing outcomes, noting that in the validation studies, AR-V7+ patients experienced a 76% survival benefit from being placed on taxane therapy versus AR-targeted therapy.

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GU ASCO Symposium 2022 Summary

by | Feb 2022

Ulka Vaishampayan, MD, Professor of Medicine and Genitourinary (GU) Oncology at the University of Michigan’s Rogel Cancer Center in Ann Arbor, Michigan, discusses highlights from the 2022 GU ASCO Symposium, focusing on advanced prostate cancer treatment research. She begins by discussing the phase 3 ARASENS trial, which looked at overall survival with darolutamide versus placebo in combination with androgen deprivation therapy (ADT) and docetaxel for metastatic hormone-sensitive prostate cancer (mHSPC). Dr. Vaishampayan explains that the investigators found that darolutamide significantly reduced the risk of death by 32.5%, and that this means that an overall survival benefit has now been seen with treatment intensification in 2 separate trials: PEACE-1 (docetaxel plus abiraterone) and ARASENS (docetaxel plus darolutamide). She argues that these results indicate that a triplet regimen with ADT, docetaxel, and darolutamide is the new standard of care in men with mHSPC. Dr. Vaishampayan then moves on to discuss the phase 3 PROpel trial of olaparib and abiraterone versus placebo and abiraterone as first-line therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). She notes that PROpel found 34% risk reduction of progression or death with olaparib plus abiraterone, and that while overall survival data is fairly immature, the trend seems to favor olaparib plus abiraterone over placebo plus abiraterone. She also highlights that the safety profile of olaparib plus abiraterone was consistent with the safety profile for the individual drugs and there was no detriment to quality of life. Finally, Dr. Vaishampayan considers first results from the phase 3 MAGNITUDE study of niraparib with abiraterone acetate and prednisone as first-line therapy in patients with mCRPC with and without homologous recombination repair (HRR) gene alterations. She explains that MAGNITUDE showed a benefit to niraparib in the HRR arm, but no benefit in the non-HRR arm. Dr. Vaishampayan concludes that MAGNITUDE demonstrates the importance of testing for HRR gene alterations in patients with mCRPC to identify who will optimally benefit from the combination of niraparib and prednisone and also supports niraparib plus prednisone as a new first-line treatment option for patients with mCRPC and alterations in genes associated with HRR.

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Point-Counterpoint: Management of mCRPC

by | Feb 2022

Rana R. McKay, MD, Associate Professor of Medicine at the University of California, San Diego, and Co-Leader of the Genitourinary Oncology Disease Team at the Moores Cancer Center, and Alan H. Bryce, MD, Medical Director of the Genomic Oncology Clinic at Mayo Clinic Arizona in Scottsdale, debate whether to treat metastatic castration-resistant prostate cancer (mCRPC).

Taking the pro position, Dr. McKay presents on why physicians need to treat mCRPC, as well as come up with additional treatment options to help improve survival for mCRPC patients. She discusses the goals of mCRPC treatment, improved quality of life and overall survival, and displays a chart that summarizes the current landscape of treatment for advanced prostate cancer as she details how androgen receptor (AR) targeting agents are enhancing treatment. Dr. McKay reviews FDA-approved agents in mCRPC, stating that the vast majority both improve overall survival and quality of life. She specifically states that the agents, outside of pembrolizumab, rucaparib, and sipuleucel-T, can potentially increase overall survival by 53.6 months and improve cancer-associated pain, disease-related urinary symptoms, and symptomatic skeletal events. Dr. McKay then shows a graph displaying mCRPC treatment in a clinical practice, suggesting that mCRPC is grossly undertreated based on the vast majority of patients not going beyond first-line treatment. She states that there is little reliable data on the cost effectiveness of treatment and concludes that mCRPC should be treated based on data showing that treatments improve overall survival and quality of life.

Taking the con position, Dr. Bryce makes an argument against treating mCRPC based on the differences between trial and real-world populations, and the challenges of extreme treatments. Dr. Bryce cites quality of life post-treatment, financial toxicity, and patient-centric treatment as cons of mCRPC treatment. He shows a graph of mCRPC treatment management in clinical practice and states that the rapid drop off after first-line therapy could be caused by patient drop outs instead of undertreatment. Dr. Bryce discusses the mCRPC treatment process in detail, focusing on how after the first line of therapy, treatment options become much more extreme and mostly consist of chemo, and most patients only have about a year left to live if they are beyond second-line treatment. He uses a case study of a 73-year-old patient to show how real-world patients can differ from selected trial patients due to how patient selection leads to optimized outcomes. Dr. Bryce reviews data showing that 20% of patients report financial toxicity, something which is associated with anxiety and depression. He concludes that clinicians should exercise prudent judgment in deciding whether or not to treat patients with advanced cancer due to trials testing beyond third-line therapy not reflecting real-world patients and financial toxicity being a significant issue.

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Point-Counterpoint: Management of mCRPC

by | Jan 2022

Rana R. McKay, MD, Associate Professor of Medicine at the University of California, San Diego, and Co-Leader of the Genitourinary Oncology Disease Team at the Moores Cancer Center, and Alan H. Bryce, MD, Medical Director of the Genomic Oncology Clinic at Mayo Clinic Arizona in Scottsdale, debate whether to treat metastatic castration-resistant prostate cancer (mCRPC).

Taking the pro position, Dr. McKay presents on why physicians need to treat mCRPC, as well as come up with additional treatment options to help improve survival for mCRPC patients. She discusses the goals of mCRPC treatment, improved quality of life and overall survival, and displays a chart that summarizes the current landscape of treatment for advanced prostate cancer as she details how androgen receptor (AR) targeting agents are enhancing treatment. Dr. McKay reviews FDA-approved agents in mCRPC, stating that the vast majority both improve overall survival and quality of life. She specifically states that the agents, outside of pembrolizumab, rucaparib, and sipuleucel-T, can potentially increase overall survival by 53.6 months and improve cancer-associated pain, disease-related urinary symptoms, and symptomatic skeletal events. Dr. McKay then shows a graph displaying mCRPC treatment in a clinical practice, suggesting that mCRPC is grossly undertreated based on the vast majority of patients not going beyond first-line treatment. She states that there is little reliable data on the cost effectiveness of treatment and concludes that mCRPC should be treated based on data showing that treatments improve overall survival and quality of life.

Taking the con position, Dr. Bryce makes an argument against treating mCRPC based on the differences between trial and real-world populations, and the challenges of extreme treatments. Dr. Bryce cites quality of life post-treatment, financial toxicity, and patient-centric treatment as cons of mCRPC treatment. He shows a graph of mCRPC treatment management in clinical practice and states that the rapid drop off after first-line therapy could be caused by patient drop outs instead of undertreatment. Dr. Bryce discusses the mCRPC treatment process in detail, focusing on how after the first line of therapy, treatment options become much more extreme and mostly consist of chemo, and most patients only have about a year left to live if they are beyond second-line treatment. He uses a case study of a 73-year-old patient to show how real-world patients can differ from selected trial patients due to how patient selection leads to optimized outcomes. Dr. Bryce reviews data showing that 20% of patients report financial toxicity, something which is associated with anxiety and depression. He concludes that clinicians should exercise prudent judgment in deciding whether or not to treat patients with advanced cancer due to trials testing beyond third-line therapy not reflecting real-world patients and financial toxicity being a significant issue.

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